tbuckley/cabot-search huggingface dataset:
Sleep, circadian biology and skeletal muscle interactions: Implications for metabolic health
Authors: Matthew Morrison, Shona L. Halson, Jonathon Weakley, John A. Hawley
Journal: Sleep Medicine Reviews (2022)

There currently exists a modern epidemic of sleep loss, triggered by the changing demands of our 21st century lifestyle that embrace 'round-the-clock' remote working hours, access to energy-dense food, prolonged periods of inactivity, and on-line social activities. Disturbances to sleep patterns impart widespread and adverse effects on numerous cells, tissues, and organs. Insufficient sleep causes circadian misalignment in humans, including perturbed peripheral clocks, leading to disrupted skeletal muscle and liver metabolism, and whole-body energy homeostasis. Fragmented or insufficient sleep also perturbs the hormonal milieu, shifting it towards a catabolic state, resulting in reduced rates of skeletal muscle protein synthesis. The interaction between disrupted sleep and skeletal muscle metabolic health is complex, with the mechanisms underpinning sleep-related disturbances on this tissue often multifaceted. Strategies to promote sufficient sleep duration combined with the appropriate timing of meals and physical activity to maintain circadian rhythmicity are important to mitigate the adverse effects of inadequate sleep on whole-body and skeletal muscle metabolic health. This review summarises the complex relationship between sleep, circadian biology, and skeletal muscle, and discusses the effectiveness of several strategies to mitigate the negative effects of disturbed sleep or circadian rhythms on skeletal muscle health.
Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: A randomized controlled trial
Authors: Jonathan Corren, David Larson, Matthew C. Altman, R. Max Segnitz, Pedro C. Avila, Paul A. Greenberger, Fuad Baroody, Mark H. Moss, Harold Nelson, Allison J. Burbank, Michelle L. Hernandez, David Peden, Sarbjit Saini, Stephen Tilles, Iftikhar Hussain, Don Whitehouse, Tielin Qin, Miguel Villarreal, Michelle Sever, Lisa M. Wheatley, Gerald T. Nepom, Srinath Sanda
Journal: Journal of Allergy and Clinical Immunology (2022)
No correlation of neutralizing antibody titers against the Omicron variant after a booster dose of COVID-19 vaccines with subsequent breakthrough Omicron infections among healthcare workers
Authors: Jeongjae Lee, Soonju Park, Ji Yeun Kim, So Yun Lim, Euijin Chang, Seongman Bae, Jiwon Jung, Min Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Nakyung Lee, David Shum, Seungtaek Kim, Youngmee Jee, Sung-Han Kim
Journal: Journal of Infection (2022)
SDCBP‐AS1 destabilizes β‐catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis
Authors: Jing Han, Menglin Nie, Cong Chen, Xiaojing Cheng, Ting Guo, Longtao Huangfu, Xiaomei Li, Hong Du, Xiaofang Xing, Jiafu Ji
Journal: Cancer Communications (2022)

Abstract Background Gastric cancer (GC) is among the most malignant tumors, yet the pathogenesis is not fully understood, especially the lack of detailed information about the mechanisms underlying long non‐coding RNA (lncRNA)‐mediated post‐translational modifications. Here, the molecular mechanisms and clinical significance of the novel lncRNA syndecan‐binding protein 2‐antisense RNA 1 (SDCBP2‐AS1) in the tumorigenesis and progression of GC were investigated. Methods The expression levels of SDCBP2‐AS1 in 132 pairs of GC and adjacent normal tissues were compared, and the biological functions were assessed in vitro and in vivo. RNA pull‐down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2‐AS1 and heterogeneous nuclear ribonucleoprotein (hnRNP) K. RNA‐sequencing, immunoprecipitation, immunofluorescence, and luciferase analyses were performed to investigate the functions of SDCBP2‐AS1. Results SDCBP2‐AS1 was significantly downregulated in GC tissues and predictive of poor patient prognosis. Silencing of SDCBP2‐AS1 promoted the proliferation and migration of GC cells both in vitro and in vivo. Mechanically, SDCBP2‐AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K and β‐catenin, thereby promoting the degradation of β‐catenin in the cytoplasm. Silencing of SDCBP2‐AS1 caused SUMOylation of hnRNP K and stabilized β‐catenin activity, which altered transcription of downstream genes, resulting in tumorigenesis and metastasis of GC. Moreover, the knockdown of hnRNP K partially abrogated the effects of SDCBP2‐AS1. Conclusions SDCBP2‐AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post‐transcriptional modifications of hnRNP K to destabilize β‐catenin. These findings suggest SDCBP2‐AS1 as a potential target for the treatment of GC.
Current updates of CRISPR/Cas9‐mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management
Authors: Khaled S. Allemailem, Mohammed A Alsahli, Ahmad Almatroudi, Faris Alrumaihi, Fahd Khaleefah Alkhaleefah, Arshad Husain Rahmani, Amjad Ali Khan
Journal: Cancer Communications (2022)

Abstract Clustered regularly interspaced short palindromic repeats‐associated protein (CRISPR/Cas9), an adaptive microbial immune system, has been exploited as a robust, accurate, efficient and programmable method for genome targeting and editing. This innovative and revolutionary technique can play a significant role in animal modeling, in vivo genome therapy, engineered cell therapy, cancer diagnosis and treatment. The CRISPR/Cas9 endonuclease system targets a specific genomic locus by single guide RNA (sgRNA), forming a heteroduplex with target DNA. The Streptococcus pyogenes Cas9/sgRNA:DNA complex reveals a bilobed architecture with target recognition and nuclease lobes. CRISPR/Cas9 assembly can be hijacked, and its nanoformulation can be engineered as a delivery system for different clinical utilizations. However, the efficient and safe delivery of the CRISPR/Cas9 system to target tissues and cancer cells is very challenging, limiting its clinical utilization. Viral delivery strategies of this system may have many advantages, but disadvantages such as immune system stimulation, tumor promotion risk and small insertion size outweigh these advantages. Thus, there is a desperate need to develop an efficient non‐viral physical delivery system based on simple nanoformulations. The delivery strategies of CRISPR/Cas9 by a nanoparticle‐based system have shown tremendous potential, such as easy and large‐scale production, combination therapy, large insertion size and efficient in vivo applications. This review aims to provide in‐depth updates on Streptococcus pyogenic CRISPR/Cas9 structure and its mechanistic understanding. In addition, the advances in its nanoformulation‐based delivery systems, including lipid‐based, polymeric structures and rigid NPs coupled to special ligands such as aptamers, TAT peptides and cell‐penetrating peptides, are discussed. Furthermore, the clinical applications in different cancers, clinical trials and future prospects of CRISPR/Cas9 delivery and genome targeting are also discussed.
Botulinum toxin for Raynaud's phenomenon associated with systemic sclerosis: comment on the article by Senet et al
Authors: Hanlin Yin, Bei Liu, Qianqian Li, Qingran Yan, Liangjing Lu
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Lancet Commission on ending stigma and discrimination in mental health
Authors: Graham Thornicroft, Charlene Sunkel, Akmal Alikhon Aliev, Sue Baker, Elaine Brohan, Rabih el Chammay, Kelly Davies, Mekdes Demissie, Joshua Duncan, Wubalem Fekadu, Petra C Gronholm, Zoe Guerrero, Dristy Gurung, Kassahun Habtamu, Charlotte Hanlon, Eva Heim, Claire Henderson, Zeinab Hijazi, Claire Hoffman, Nadine Hosny, Fiona-Xiaofei Huang, Sarah Kline, Brandon A Kohrt, Heidi Lempp, Jie Li, Elisha London, Ning Ma, Winnie W S Mak, Akerke Makhmud, Pallab K Maulik, Maria Milenova, Guadalupe Morales Cano, Uta Ouali, Sarah Parry, Thara Rangaswamy, Nicolas Rüsch, Taha Sabri, Norman Sartorius, Marianne Schulze, Heather Stuart, Tatiana Taylor Salisbury, Norha Vera San Juan, Nicole Votruba, Petr Winkler
Journal: The Lancet (2022)
Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death
Authors: Michael Bretthauer, Magnus Løberg, Paulina Wieszczy, Mette Kalager, Louise Emilsson, Kjetil Garborg, Maciej Rupinski, Evelien Dekker, Manon Spaander, Marek Bugajski, Øyvind Holme, Ann G. Zauber, Nastazja D. Pilonis, Andrzej Mroz, Ernst J. Kuipers, Joy Shi, Miguel A. Hernán, Hans-Olov Adami, Jaroslaw Regula, Geir Hoff, Michal F. Kaminski
Journal: New England Journal of Medicine (2022)

Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear.We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause.Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04).In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).
Understanding the Results of a Randomized Trial of Screening Colonoscopy
Authors: Jason A. Dominitz, Douglas J. Robertson
Journal: New England Journal of Medicine (2022)

For more than two decades, colonoscopy has been recommended as one of several available options for colorectal cancer screening, and it has been the predominant form of screening for colorectal cancer used in the United States. However, the best evidence to support its use has been limited to data from cohort studies, which have estimated that this type of screening has been associated with a 40 to 69% decrease in the incidence of colorectal cancer and a 29 to 88% decrease in the risk of death from this disease.1 Unlike randomized, controlled trials, which have provided support for fecal occult . . .
A predictive mechanistic model of drug release from surface eroding polymeric nanoparticles
Authors: Rebeca T. Stiepel, Erik S. Pena, Stephen A. Ehrenzeller, Matthew D. Gallovic, Liubov M. Lifshits, Christopher J. Genito, Eric M. Bachelder, Kristy M. Ainslie
Journal: Journal of Controlled Release (2022)
Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Lukas Leiendecker, Tobias Neumann, Pauline S. Jung, Shona M. Cronin, Thomas L. Steinacker, Alexander Schleiffer, Michael Schutzbier, Karl Mechtler, Thibault Kervarrec, Estelle Laurent, Kamel Bachiri, Etienne Coyaud, Rajmohan Murali, Klaus J. Busam, Babak Itzinger-Monshi, Reinhard Kirnbauer, Lorenzo Cerroni, Eduardo Calonje, Arno Rütten, Frank Stubenrauch, Klaus G. Griewank, Thomas Wiesner, Anna C. Obenauf
Journal: Cancer Discovery (2022)

Abstract The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, “low-risk” HPV, recapitulates the molecular hallmarks of oncogenic, “high-risk” HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell–like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell–like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers. Significance: We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell–like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers. See related commentary by Starrett et al., p. 17. This article is highlighted in the In This Issue feature, p. 1
Stem cell microencapsulation maintains stemness in inflammatory microenvironment
Authors: Yajun Zhao, Yilin Shi, Huiqi Yang, Mengmeng Liu, Lanbo Shen, Shengben Zhang, Yue Liu, Jie Zhu, Jing Lan, Jianhua Li, Shaohua Ge
Journal: International Journal of Oral Science (2022)

Abstract Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe III /tannic acid coordination network to obtain spheroid@[Fe III -TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
IFT140+/K14+ cells function as stem/progenitor cells in salivary glands
Authors: Xueming Zhang, Ji Zhou, Xinyu Wang, Jiangyu Geng, Yubei Chen, Yao Sun
Journal: International Journal of Oral Science (2022)

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14+ (K14+) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14+ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140+/ K14+ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14+ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14+ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140+/K14+, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
“Shopping around” for treatment is not a solution to cancer backlog
Authors: Ajay Aggarwal, Fiona M Walter, Richard Sullivan, Jan van der Meulen
Journal: BMJ (2022)

<h3>Objective</h3> The aim of this study was to determine the burden and risk factors of prediabetes and diabetes in the general adult population of Luxembourg. <h3>Design</h3> Cross-sectional survey between 2013 and 2015. <h3>Setting</h3> Data were collected as part of the European Health Examination Survey in Luxembourg (EHES-LUX). <h3>Participants</h3> 1451 individuals were recruited in a random sample of the 25–64-year-old population of Luxembourg. <h3>Outcomes</h3> Diabetes was defined by a glycaemic biomarker (fasting plasma glucose (FPG) ≥7.0 mmol/L), self-reported medication and medical diagnosis; prediabetes by a glycaemic biomarker (FPG 5.6–6.9 mmol/L), no self-reported medication and no medical diagnosis. Undiagnosed diabetes was defined only from the glycaemic biomarker; the difference between total and undiagnosed diabetes was defined as diagnosed diabetes. Odds of diabetes and prediabetes as well as associated risk factors were estimated. <h3>Results</h3> The weighted prevalence of prediabetes and diabetes was 25.6% and 6.5%, respectively. Nearly 4.8% (men: 5.8%; women: 3.8%) were diagnosed diabetes and 1.7% (men: 2.6%; women: 0.7%) were undiagnosed diabetes. The multivariable-adjusted OR (MVOR) for diabetes risk were: age 1.05 (95% CI 1.01 to 1.09), family history of diabetes 3.24 (1.95–5.38), abdominal obesity 2.63 (1.53–4.52), hypertension 3.18 (1.76–5.72), one-unit increase of triglycerides 1.16 (1.10–1.22) and total cholesterol 0.74 (0.64–0.86). The MVOR for prediabetes risk were: age 1.04 (95% CI 1.02 to 1.06), male sex 1.84 (1.30–2.60), moderate alcohol consumption 1.38 (1.01–1.89), family history of diabetes 1.52 (1.13–2.05), abdominal obesity 1.44 (1.06–1.97), second-generation immigrants 0.61 (0.39–0.95) and a one-unit increase of serum high-density lipoprotein cholesterol 0.70 (0.54–0.90). <h3>Conclusions</h3> In Luxembourg, an unexpectedly high number of adults may be affected by prediabetes and diabetes. Therefore, these conditions should be addressed as a public health priority for the country, requiring measures for enhanced detection and surveillance, which are currently lacking, especially in primary care settings.
Management of chronic migraine
Authors: Alexandra Hovaguimian, Julie Roth
Journal: BMJ (2022)

ABSTRACT Chronic migraine is a neurologic disorder associated with considerable disability, lost productivity, and a profound economic burden worldwide. The past five years have seen a dramatic expansion in new treatments for this often challenging condition, among them calcitonin gene related peptide antagonists and neuromodulatory devices. This review outlines the epidemiology of and diagnostic criteria and risk factors for chronic migraine. It discusses evidence based drug and non-drug treatments, their advantages and disadvantages, and the principles of patient centered care for adults with chronic migraine, with attention to differential diagnosis and comorbidities, clinical reasoning, initiation and monitoring, cost, and availability. It discusses the international guidelines on drug treatment for chronic migraine and evaluates non-drug treatments including behavioral and complementary therapies and lifestyle modifications. Finally, it discusses the management of chronic migraine in special populations, including pediatrics, pregnancy, and older people, and considers future questions and emerging research in the field.
Allergic airway inflammation delays glioblastoma progression and reinvigorates systemic and local immunity in mice
Authors: Aurélie Poli, Anaïs Oudin, Arnaud Muller, Ilaria Salvato, Andrea Scafidi, Oliver Hunewald, Olivia Domingues, Petr V. Nazarov, Vincent Puard, Virginie Baus, Francisco Azuaje, Gunnar Dittmar, Jacques Zimmer, Tatiana Michel, Alessandro Michelucci, Simone P. Niclou, Markus Ollert
Journal: Allergy (2022)

Numerous patient-based studies have highlighted the protective role of immunoglobulin E-mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection.An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1-KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA-sequencing. Peripheral as well as tumor-associated immune cells were characterized by flow cytometry. The impact of allergy-related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets.We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro-inflammatory-like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T-cells in the circulation as well as tumor-infiltrating CD4+ T-cells. The survival benefit conferred by AAI was lost in mice devoid of adaptive immunity.Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy-induced immune protection against GBM.